COVER STORY: USA’s research includes studies on health, manufacturing and technology

At any given point, researchers at the University of South Alabama could be working on something groundbreaking with implications in the realms of industry, medicine or even the fine arts. At a comprehensive research university like USA, research can take on many forms and is usually a collaborative effort between faculty from multiple disciplines, students and occasionally intellectual property lawyers.

From targeting cells specifically related to cancer growth to perfecting new forms of glass blowing, there are many types, stages and benefactors of the university’s academic research.

“It’s difficult to quantify, but including what’s funded and unfunded and some of the student research, I feel comfortable saying there’s close to 1,000 different projects going at any give time,” Lynne Chronister, vice president for research and economic development said. “The ideas for those projects could come from having a beer at Mellow Mushroom — and some of them do — or they might come from a specific request for proposals from the federal government or the connections we have with industry.”

Many universities have long been paired with centers for research but creating patented products and processes wasn’t always as common as it is today, and Chronister credits a change by the federal government in the ‘80s with helping to capitalize from their work.

“Before then, if the federal government funded any research — they owned it,” she said. “University research projects were going into a final report stage and then they would never go anywhere because there was no incentive.”

For universities like USA, which gets around 75 percent of its research funding from the federal government, being able to retain ownership of intellectual property created a lot more incentive to pursue research projects.

Since 1998, USA has received nearly $162 million in direct federal appropriations for research and outreach, but public monies aren’t the only source of funding.

In 2014, USA received just under $60 million in grants and external contracts with industry partners, which does include federal funding. Chronister said this type of funding has helped change the perception of universities from isolated places of learning to “true economic engines.”

“The university has in the last couple of years been focused on really supporting our community, and that’s been enhanced and emphasized by our new President Dr. Tony Waldrop,” she said. “We are a part of our community. We’re one of the largest employers, and we want to make sure we’re contributing.”

Each year, USA brings in more than $2 million in licensing revenue from academic innovations it owns a stake in, money that is typically used to fund other ongoing research.

Those funds are derived from the patents it shares with inventors and the equity it has in companies created by those inventors or in separate companies that have licensed a product or process developed at USA.

“We have the authority to try to license our intellectual property out, which we would generally do for a portion of any future royalties or an equity interest,” Chronister said. “We usually wouldn’t (retain) more than a 5 percent interest in a startup, but when a company is first started it might be 10 or 15 percent, but then we would dilute it down as more investors become involved.”

Because the university uses public funds, Chronister said USA doesn’t invest in private companies but licenses products or ideas that the university has patented. Another option is to enable a new business to be established, sometimes by the inventor using USA technology. This opens the door to other types of funding.

Chronister said “angel funding” is one of the first sources of outside private funding a startup normally receives.

The Gulf Coast Angel Network, an angel investment group specializing in the area, defines an angel as “a high net-worth individual who invests his or her own money in start-up companies in exchange for an equity share of the businesses.”

Unless the inventors decide to sell the company to larger entity, Chronister said the next and largest step in private funding usually comes from venture capital groups.

“Anything can help us get the word out on new technology, a company may even see something in a press release or the faculty may have industry contacts,” she said. “I would say there’s about a 50/50 split of industries coming to us and us going to them.”

Andrew Byrd oversees intellectual property management for USA and works closely with faculty to bridge the gap between laboratory research and the business world.

“Traditionally, researchers view submitting an invention disclosure to the office of Intellectual Property Management (IPM) as their ‘finish line,’” Byrd said. “In reality, it is the starting line of a partnership and a process between the inventor and our office.”

According to Byrd, his office gets involved when researchers think they’re working on something with commercial value and when it comes to inventions, he said one of the first steps is determining if there’s a market for the product.

Chronister said developing those products and processes could ultimately help USA become a “Research University: Very High (RU/VH), as defined by the Carnegie Classifications. Currently, USA is considered — like Auburn University and the University of Alabama — as a Research University: High (RU/H).

The only RU/VH in the state are the University of Alabama at Huntsville and Birmingham, but Chronister said over time, USA hopes change that by increasing its number of doctoral programs and successful research projects.

Z-Aligned Fiber Reinforced Polymer (Kuang-Ting Hsiao, Greg Hickman)

The aerospace industry has been using carbon fiber composites for some time now, and Dr. Kuang-Ting Hsiao, professor of mechanical engineering at USA, said engineers have been trying to address weaknesses in the material’s “Z direction” for more than a decade.

Dr. Kuang-Tin Hsaio demonstrates a carbon fiber panel at the Unversity of South Alabama recently.

Fiber reinforced polymers are made from layers of carbon fiber strands that overlap. When coated with epoxy and heated, the layers form a composite material that is 10 to 30 times stronger than steel at only 20 percent of the weight.

According to John Steadman, Dean of the College of Engineering, the composites are very strong and resilient on the surface direction, but are very weak from the Z direction, which runs perpendicular to the layers of carbon fiber.

“If something is trying to delaminate and separate the material, it’s not nearly as strong because you don’t have any carbon in that direction,” Steadman said. “Dr. Hsiao has developed a process that allows us to put in nano scale fibers and align them in the Z direction.”

In simple terms, the product adds an additional direction of carbon fiber that runs perpendicular to the interwoven layers stacked on top of one another in existing carbon fiber manufacturing, increasing its durability and ease of repair without adding weight.

Hsiao’s process, though currently patent pending, is how Hsiao and his students are producing the Z-aligned materials, but Hsiao said getting to that stage to took more than a decade of refining his idea and finding funding for the necessary research.

“In 2003 I started thinking about the material and process, but it wasn’t a fully mature idea,” Hsiao said. Then in 2007, I started calling different agencies (for funding).”

In 2009, Hsiao obtained nearly $1 million from NASA to test the feasibility of his design, but not before being rejected by both the U.S. Navy and U.S. Air Force for grant proposals, both of which told Hsiao, “it cannot be done.”

Though Hsiao has been able to create the Z-aligned FRP and establish a manufacturing process consistent with existing mass-production techniques, he said his research isn’t finished.

“Right now we want to create more samples for testing to try and get it perfect,” he said. “We’re testing the thermal and electrical properties of the material.”

Those tests are aimed at proving one possible benefit of the material, the added conductivity of additional carbon fibers running parallel to the ones already in existing composites. Because the conductive Z-aligned carbon fibers would carry electricity through the epoxy, Hsiao’s design may not require an outer metal mesh, which would significantly reduce the weight of the final product.

Steadman said once the product is perfected, the next step for Z-aligned carbon fiber is trying to find an industry partner to take the idea to the next level. He did say there is a significant demand for carbon fiber products in aerospace industries and for other products like golf clubs and lightweight racing bicycles.

“The key to making this all really happen is to make sure you get it in the hands of a truly innovative and forward-thinking company who will produce and make use of it,” Steadman said. “Occasionally, you get a company that purchases a product like this only for the purpose of keeping you from getting it on the market, and we’ll try very hard to make sure that doesn’t happen to us.”

Real-Time Hyperspectral Imaging (Silas Leavesley, Thomas Rich)

Dr. Thomas Rich, associate professor of pharmacology, and Dr. Silas Leavesley, associate professor of chemical and bimolecular engineering, have been working together on an imaging device for around six years — something that could drastically shorten the time it takes to perform some of medicine’s more unpleasant procedures.

While the human eye is limited to the visible spectrum, hyperspectral imaging divides the electromagnetic spectrum into many more bands that can be utilized more effectively for medical assessment and diagnosis.

“We were trying to figure out a way to take spectral imaging and design a technology to speed it up so it could operate much faster,” Leavesley said. “We’ve done that by changing the wavelengths (colors) of light we illuminate with.”

Leavesly said illuminating human tissues with white light— the method used most commonly — produces a low power image because only a small portion of the light spectrum is detected.

Hyperspectral imaging at many wavelengths allows physicians to illuminate with a specific color and collect the entire spectrum, before illuminating with another color, which has shown to reveal specific anomalies in tissue samples.

“We have images that are easily collected between five to 100 (times) faster depending on exactly what wavelengths we use and what molecule we’re looking at,” Rich said. “We’re able to quantify the signal-to-noise ratio in the sample images we take. With high signal, low noise, you discriminate the molecular components of the sample more cleanly.”

According to Leavesley, the technology is capable of moving through 32 images in less than a 30th of a second. In other words, it is processing the images from 32 wavelengths 30 times each second.

“It will look like you’re navigating at a video frame rate,” Leavesley said. “If you’ve got more signal, instead of acquiring an image in 100 milliseconds, you can acquire it in 10 milliseconds or one millisecond.”

That type of speed is very useful when you’re working inside the human body because those procedures can typically be uncomfortable. It can also be difficult for clinicians to keep patients from moving, which can distort the images collected.

The pair said the technology could have multiple nonmedical and medical uses, but their focus has been on improving gastrointestinal imaging, specifically colonoscopies. Those procedures are done quickly, and improving imaging capability increases both speed and the ability to detect cancerous or precancerous cells.

“Colonoscopy is the obvious choice,” Rich said. “You don’t want that to be a two hour procedure.”

The theory is that additional information in the images from a functioning endoscope outfitted with the technology will allow doctors to detect cancerous lesions earlier and more accurately.

Currently the device is hooked up to a microscope system, but in the next year they hope to connect it to an endoscope system — one of the milestones the team outlined in its application to the 2014 Alabama Launchpad Competition, which helps fund Alabama businesses with a high potential for growth.

SpectraCyte, the startup founded by Rich and Leavesley, took home $87,000 from this year’s competition Sept. 26, which was the second largest award given this year. They’re hoping to use that money get their microscope-based system up and running.

“Think, research labs,” Leavesley said. “The more long-term and more expensive goal is a clinical endoscope, but some of what we do on the microscope should help fund that.”

In the next three years, SpectraCyte plans to have an endoscope on a cart that can be tested at USA’s medical facilities, and with approval from the Food and Drug Administration they hope to have devices at other facilities within the next five years.

Both Rich and Leavesley said the collaborative nature of the university helped foster the success they’ve seen in their research. That includes the two colleagues from different disciplines and the assistance the company got from USA’s intellectual property office when it came time to start their business.

“I think that is under appreciated even by the people at South sometimes,” Rich said. “I’ve been lots of places and this is by far the most collaborative environment I’ve ever been in. It’s the reason I came here.”

PP5 Protein Inhibitor (Dr. Richard Honkanen)

For more than two decades, Dr. Richard Honkanen, professor of biochemistry at the USA College of Medicine, has been looking at tumor cells to determine what was unique about them.

Honkanen and others working on this type of research eventually discovered that the protein “PP5” is over-expressed in human breast cancer, but it took almost another five years just to figure out what it actually did.

“At first we didn’t know what it was, but we cloned it and realized it was an enzyme, actually a phosphatase,” he said. “From what we think, its job is to allow cells to survive under transient periods of low oxygen, which is one of thing that is normally very limiting for cell growth.”

Honkanen said there are typically seven or eight genes that have to be defective to make an otherwise normal cell cancerous, and high levels of PP5 are what help metastatic tumors develop in breast cancer patients.

That’s why Honkanen, his students and researchers at several other institutes like Scripps University, the University of Kansas and the University of Alabama at Birmingham have been working to develop a PP5 inhibitor.

That group of researchers includes medicinal chemists and crystallographers that create surface models of purified PP5 crystals using X-ray crystallography. This allows chemists to look at versions of the enzyme on a molecular level, which helps develop more specific compounds.

“When you develop antibiotics you find something in a bacteria it needs to survive that we don’t have and create a drug that kills that,” Honkanen said. “Cancer cells are human cells gone amok, so you have to find something that’s really specific so it’s only toxic to the tumor cells.”

However, to get a compound tailored, it specifically requires high quality models of the enzyme, which is why a PP5 protein developed by Honkanen and other researches at USA was sent to the International Space Station earlier this year.

According to Honkanen, the crystals — formed when water is evaporated from a concentrated protein solution — are packed more uniformly in microgravity, which is why USA’s PP5 was one of 92 proteins chosen to be grown into crystals on the ISS. Some of that data has already been sent back to Honkanen.

“It’s a blinded study so nobody who analyzes the data is going to know if it was made in space or on Earth,” he said. “They’re trying to decide if this is really worth doing. Ultimately, if the data’s good, they may try to put an X-ray beam up on the space station.”

Though the data he’s received back has been good, chemists at USA are still working to develop a PP5 inhibitor that doesn’t inhibit the other seven proteins in the PPP family, which can have toxic effects on humans.

Researchers have been able to completely delete the PP5 gene from mice, and Honkanen said he’s working on funding to help study effects of introducing breast cancer to a mouse that’s had the gene removed. In the meantime, all of the data from the crystals grown on the ISS should be available in May 2015.

Honkanen said if a non-toxic inhibitor is eventually developed, the process of making the compound into a drug would likely move forward fairly quickly.

“We’d have to do all the animal toxicity testing models, but clinical testing these days is about $200 million, so we’d turn it over to a pharmaceutical company at that point,” he said.

About The Author

Jason Johnson originally hails from Elba, Alabama, and graduated summa cum laude from Troy University in 2011. He’s been a reporter for Lagniappe since 2014, where he covers an array of topics with a focus on county government, local courts and education.
Previously, Jason worked for the Southeast Sun (Enterprise, Alabama), the Alexander City Outlook and 94.7 WTBF FM (Troy, Alabama).
He’s also been recognized by the Alabama Press Association with designations in general excellence, photography and education reporting. In his spare time, Jason is a guitarist and drummer who enjoys the benefit of regularly playing with musicians better than himself.